[Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units]. / Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

[Management of infectious complications associated with coronavirus infection in severe patients admitted to ICU]. / Manejo de las complicaciones infecciosas asociadas con la infección por coronavirus en pacientes graves ingresados en UCI.

Infections have become one of the main complications of patients with severe SARS-CoV-2 pneumonia admitted in ICU. Poor immune status, frequent development of organic failure requiring invasive supportive treatments, and prolonged ICU length of stay in saturated structural areas of patients are risk factors for infection development. The Working Group on Infectious Diseases and Sepsis GTEIS of the Spanish Society of Intensive Medicine and Coronary Units SEMICYUC emphasizes the importance of infection prevention measures related to health care, the detection and early treatment of major infections in the patient with SARS-CoV-2 infections. Bacterial co-infection, respiratory infections related to mechanical ventilation, catheter-related bacteremia, device-associated urinary tract infection and opportunistic infections are review in the document.

Ventilator-associated pneumonia by methicillin-susceptible Staphylococcus aureus: do minimum inhibitory concentrations to vancomycin and daptomycin matter?

The use of vancomycin minimum inhibitory concentration (MIC) as an outcome predictor in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia has become an important topic for debate in the last few years. Given these previous results, we decided to investigate whether MICs to vancomycin or daptomycin had any effect on the evolution of patients with ventilator-associated pneumonia (VAP) due to MSSA. An observational, retrospective, multicenter study was conducted among patients with MSSA VAP. We analyzed the relationship between vancomycin and daptomycin MICs and early clinical response (72 h), 30-day mortality, intensive care unit (ICU) length of stay (LOS), and duration on mechanical ventilation. Univariate and multivariate analyses were performed. Sixty-six patients from 12 centers were included. Twenty-six patients (39%) had an infection due to MSSA strains with a vancomycin MIC ≥1.5 µg/mL. Daptomycin MIC was determined in 58 patients, of whom 17 (29%) had an MIC ≥1.0 µg/mL. Ten patients (15%) did not respond to first-line treatment. Only daptomycin MIC ≥1.0 µg/mL had a significant association [odds ratio (OR): 30.00; 95% confidence interval (CI): 2.91-60.41] with early treatment failure. The 30-day mortality was 12% (n = 8). Any variable was associated with mortality in the multivariate analysis. None of the variables studied were associated with ICU LOS or duration on mechanical ventilation. In patients with MSSA VAP, vancomycin MIC does not influence the response to antibiotic treatment or the 30-day mortality. Daptomycin MIC was directly related to early treatment failure.

Impact of the implementation of a Sepsis Code hospital protocol in antibiotic prescription and clinical outcomes in an intensive care unit. / Impacto de la implantación de un Código Sepsis intrahospitalario en la prescripción de antibióticos y los resultados clínicos en una unidad de cuidados intensivos.

INTRODUCTION: A study was performed to analyze the impact of an in-hospital Sepsis Code (SC) program on use of antibiotic and clinical outcomes. DESIGN: Quasi-experimental observational retrospective study. SETTING: Polyvalent 11 beds ICU belonging to a tertiary Universitary hospital. PATIENTS: Patients admitted consecutively to the ICU with diagnosis of severe sepsis or septic shock. INTERVENTIONS: A post intervention group (POST-SC) (September 2012-August 2013) was compared with a historical group (PRE-SC) used as control (January-December 2010). VARIABLES: Antibiotic treatment, therapeutic antibiotic strategy, mortality and length of stay. Antibiotic consumption was expressed as defined daily doses (DDD)/ 100 stays. RESULTS: 42 patients with SS/SS in POST-SC group and 50 patients in PRE-SC group were consecutively recluted and further analyzed. Total antibiotic consumption (DDD) was similar in both groups. Rate of de-escalation therapy was significantly higher in POST-SC group (75% vs 30,8%, p<0,005) while prescription of restricted antibiotics was significantly lower (74% vs 52%, p=0,031). Finally POST-SC patients showed a significantly decrease in hospital and 28 days mortality rates [23% vs 44%, (p=0,035) and 31% vs 56% (p=0,014) respectively] as well as a reduction in ICU length of stay compared to PRE-SC cohort (5 days vs 10,5 days, p=0,05). CONCLUSION: The implementation of a Sepsis Code-hospital protocol is associated to an improvement in the management of antibiotic therapy with a significant increase in de-escalation therapy and lesser utilization of restricted use antibiotics, as well as a significant reduction in mortality, and a tendency towards shorter ICU length stay.

Immunoglobulins IgG1, IgM and IgA: a synergistic team influencing survival in sepsis.

OBJECTIVE: The impact of endogenous immunoglobulin isotypes on the prognosis of patients with severe sepsis has not been sufficiently explored. The aim of this study was to evaluate the association between immunoglobulin levels in plasma and survival in patients with this condition. DESIGN AND PATIENTS: A prospective multicentre cohort study was conducted. A total of 172 adult patients admitted to the intensive care unit (ICU) with severe sepsis or septic shock were recruited. Patients were classified based on deciles of immunoglobulin concentrations at diagnosis of sepsis. Categorical variables were created and tested for their association with survival during hospitalization in the ICU. RESULTS: Overall, 42 patients died in the ICU during the study. Kaplan-Meier analysis showed that immunoglobulin concentrations below 300 mg dL(-1) for IgG1, 35 mg dL(-1) for IgM and 150 mg dL(-1) for IgA were associated with shorter survival times. Multivariate regression analysis showed that IgG1 < 300 mg dL(-1) was a risk factor for mortality [odds ratio (OR) 2.50, 95% confidence interval (CI) 1.04-6.03; P = 0.042]. The combined presence of IgG1, IgM and IgA levels below the described thresholds had a synergistic impact on mortality risk (OR 5.27, 95% CI 1.41-19.69; P = 0.013). A similar effect was observed for combined low levels of IgG1 and IgA (OR 4.10, 95% CI 1.28-13.12; P = 0.018) and also of IgG1 and IgM (OR 3.10. 95% CI 1.13-8.49; P = 0.028). CONCLUSIONS: The combined presence of low levels of the endogenous immunoglobulins IgG1, IgM and IgA in plasma is associated with reduced survival in patients with severe sepsis or septic shock. Assessment of the concentrations of these immunoglobulins could improve the results of treatment with exogenous immunoglobulins in patients with sepsis.

Prevalence of nonalcoholic fatty liver disease in a Spanish town: a population-based study.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is western countries' most important cause of hepatic steatosis and hypertransaminasemia. The objective was to evaluate the prevalence of NAFLD among 261,025 people in the East Valladolid public healthcare area in Spain. METHODS: We randomly selected 1800 participants from a public healthcare system card database, representing most of the population. We performed a medical record, measurement of anthropometric parameters, abdominal ultrasound, and blood tests to rule out hepatic disease in all patients. We calculated the FLI score in all patients. RESULTS: 448 participants agreed to participate in the study. The prevalence of nonalcoholic fatty liver disease in our study was 22.3% [18.5%-26.2%]. Prevalence was highest between 50 and 70 years, increasing with age (p < 0.006). There were no significant differences in sex (p = 0.338). The median Body mass index was 27.2, and NAFLD was related to the weight (p < 0,001) and abdominal perimeter (p < 0.001). Logistic regression analysis showed GGT lower than 26 UI/ml, body mass index higher than 31, and HOMA IR greater than 2.54 as independent factors to predict NAFLD in the sample. NAFLD diagnosis matched with an elevated FLI score in 88% of cases. CONCLUSION: According to other epidemiological studies, NAFLD's prevalence is very high. A complete study with a clinical consultation, image studies, and blood tests in all patients allows us to assess the prevalence of NAFLD in the population.

Influence of epidemiological and clinical factors in the reactogenicity to Comirnaty® vaccine in health care workers of a Spanish university teaching hospital (COVIVAC study).

OBJECTIVE: Comirnaty® is an mRNA vaccine against COVID-19 which has been administered to millions of people since the end of 2020. Our aim was to study epidemiological and clinical factors influencing reactogenicity and functional limitation after the first two doses of the vaccine in health care workers (HCWs). METHODS: Prospective post-authorization cohort study to monitor safety and effectiveness of the vaccine. RESULTS: Local side effects were mild and presented both with first and second dose of Comirnaty. Systemic side effects were more frequent after 2nd dose. Nevertheless, previous SARS-CoV-2 infection was associated with systemic effects after the first dose of the vaccine (OR ranging from 2 to 6). No severe adverse effects were reported. According to multivariate analysis, the degree of self-reported functional limitation after the first dose increased with age, female sex, previous COVID-19 contact, previous SARS-CoV-2 infection, and Charlson Comorbidity Index (CCI). After the second dose, the degree of functional limitation observed was lower in those with previous SARS-CoV-2 infection, and it was positively associated to the degree of functional limitation after the first dose. CONCLUSIONS: Systemic adverse effects were more frequent after the second dose of Comirnaty. Previous SARS-CoV-2 infection was associated with systemic effects after the first dose. Age, female sex, previous COVID-19, previous isolation due to COVID-19 contact, and CCI showed to be independent predictors of the degree of functional limitation after the 1st dose of Comirnaty®. After the 2nd dose, the degree of functional limitation was lower in those who previously had SARS-CoV-2 infection.

[Vasoactive drugs in the treatment of septic shock]. / Fármacos vasoactivos en el tratamiento del shock séptico.

Septic shock is a high mortality complication frequently associated with sepsis. Early initiation of vasopressor treatment, even before completion of initial fluid resuscitation, is a determining factor in prognosis. In this sense, norepinephrine continues to be the drug of first choice, although there is increasing evidence of benefit combining it with other non-adrenergic drugs, such as vasopressin, instead of escalating norepinephrine doses. The pathophysiology of septic shock is multifactorial, and sometimes is associated with a situation of myocardial dysfunction that contributes to hemodynamic instability. It is essential to identify this situation since it worsens the prognosis and may benefit from combined treatment with inotropic drugs. There are novel vasoactive agents under study, more selective than the classic ones that in a next future could help to design more individualized and precise treatments. In the present work, the current knowledge about vasoactive drugs and their use in the management of septic shock is summarized according to the most recent scientific evidence.

Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Management of infectious complications associated with coronavirus infection in severe patients admitted to ICU. / Manejo de las complicaciones infecciosas asociadas con la infección por coronavirus en pacientes graves ingresados en UCI.

Infections have become one of the main complications of patients with severe SARS-CoV-2 pneumonia admitted in ICU. Poor immune status, frequent development of organic failure requiring invasive supportive treatments, and prolonged ICU length of stay in saturated structural areas of patients are risk factors for infection development. The Working Group on Infectious Diseases and Sepsis GTEIS of the Spanish Society of Intensive Medicine and Coronary Units SEMICYUC emphasizes the importance of infection prevention measures related to health care, the detection and early treatment of major infections in the patient with SARS-CoV-2 infections. Bacterial co-infection, respiratory infections related to mechanical ventilation, catheter-related bacteremia, device-associated urinary tract infection and opportunistic infections are review in the document.

Management of infectious complications associated with coronavirus infection in severe patients admitted to ICU.

Infections have become one of the main complications of patients with severe SARS-CoV-2 pneumonia admitted in ICU. Poor immune status, frequent development of organic failure requiring invasive supportive treatments, and prolonged ICU length of stay in saturated structural areas of patients are risk factors for infection development. The Working Group on Infectious Diseases and Sepsis GTEIS of the Spanish Society of Intensive Medicine and Coronary Units SEMICYUC emphasizes the importance of infection prevention measures related to health care, the detection and early treatment of major infections in the patient with SARS-CoV-2 infections. Bacterial co-infection, respiratory infections related to mechanical ventilation, catheter-related bacteremia, device-associated urinary tract infection and opportunistic infections are review in the document.

[Analysis of early tracheostomy and its impact on development of pneumonia, use of resources and mortality in neurocritically ill patients]. / Análisis de la traqueotomía precoz y su impacto sobre la incidencia de neumonía, consumo de recursos y mortalidad en pacientes neurocríticos.

OBJECTIVE: We analyze the most suitable time to perform tracheostomy in neurocritically ill patients. We compare morbimortality and use of resources between those patients in which tracheostomy was done early (9 days), in a selected group of patients. MATERIAL AND METHODS: We made an observational prospective study involving a group of patients diagnosed as traumatic brain injury (TBI) or stroke, whose tracheostomy was performed during their stay at the Intensive Care Unit. We compared two groups: a) early tracheostomy (during first 9 days of ICU stay); b) late tracheostomy (made on 10th day or later). As variables, we studied: demographic data, severity of illness at admission, admittance department, diagnosis, length of intubation, length of mechanical ventilation (LMV), sedation and antibiotic treatment needs, ventilator-associated pneumonia (VAP) events, ICU length of stay and mortality. We calculated relative risk of suffering from pneumonia and made a multivariate logistic regression to establish which factors were associated with an increased risk of developing pneumonia. Statistical signification p

Endothelial dysfunction is an early indicator of sepsis and neutrophil degranulation of septic shock in surgical patients.

BACKGROUND: Stratification of the severity of infection is currently based on the Sequential Organ Failure Assessment (SOFA) score, which is difficult to calculate outside the ICU. Biomarkers could help to stratify the severity of infection in surgical patients. METHODS: Levels of ten biomarkers indicating endothelial dysfunction, 22 indicating emergency granulopoiesis, and six denoting neutrophil degranulation were compared in three groups of patients in the first 12 h after diagnosis at three Spanish hospitals. RESULTS: There were 100 patients with infection, 95 with sepsis and 57 with septic shock. Seven biomarkers indicating endothelial dysfunction (mid-regional proadrenomedullin (MR-ProADM), syndecan 1, thrombomodulin, angiopoietin 2, endothelial cell-specific molecule 1, vascular cell adhesion molecule 1 and E-selectin) had stronger associations with sepsis than infection alone. MR-ProADM had the highest odds ratio (OR) in multivariable analysis (OR 11·53, 95 per cent c.i. 4·15 to 32·08; P = 0·006) and the best area under the curve (AUC) for detecting sepsis (0·86, 95 per cent c.i. 0·80 to 0·91; P < 0·001). In a comparison of sepsis with septic shock, two biomarkers of neutrophil degranulation, proteinase 3 (OR 8·09, 1·34 to 48·91; P = 0·028) and lipocalin 2 (OR 6·62, 2·47 to 17·77; P = 0·002), had the strongest association with septic shock, but lipocalin 2 exhibited the highest AUC (0·81, 0·73 to 0·90; P < 0·001). CONCLUSION: MR-ProADM and lipocalin 2 could be alternatives to the SOFA score in the detection of sepsis and septic shock respectively in surgical patients with infection.

ANTECEDENTES: La estratificación de la gravedad de una infección se basa actualmente en la puntuación SOFA (Sequential Organ Failure Assessment), que es difícil de calcular fuera de la unidad de cuidados intensivos. Los biomarcadores podrían ayudar a estratificar la gravedad de la infección en pacientes quirúrgicos. MÉTODOS: Se compararon las concentraciones de 10 biomarcadores que denotan disfunción endotelial, 22 que indican granulopoyesis de emergencia y 6 que expresan la degranulación de neutrófilos en tres grupos de pacientes de tres hospitales españoles (100 con infección, 95 con sepsis y 57 con shock séptico) en las primeras doce horas después del diagnóstico. RESULTADOS: Siete biomarcadores que expresan disfunción endotelial (proadrenomedulina, sindecan-1, trombomodulina, angiopoyetina-2, endocan-1, molécula de adhesión endotelial 1 y E-selectina) mostraron una fuerte asociación con la sepsis en comparación con la infección aislada. La proadrenomedulina presentó el valor más alto de la razón de oportunidades (odds ratio, OR) en el análisis multivariable (OR 11,53, i.c. del 95% 4,15-32,08, P = 0,006) y la mejor área bajo la curva para detectar sepsis (AUC 0,86, i.c. del 95% 0,80-0,91, P < 0,001). En la comparación entre sepsis y shock séptico, los biomarcadores que mostraron la asociación más estrecha con el shock séptico fueron dos biomarcadores de degranulación de neutrófilos (proteinasa-3 y lipocalina-2) (OR 8,09, i.c. del 9% 1,34-48,91, P = 0,028; OR 6.62, i.c. del 95% 2,47-17,77, P = 0,002), pero la lipocalina-2 presentó la mejor AUC (0,81, i.c. del 95% 0,73-0,90, P < 0,001). CONCLUSIÓN: la proadrenomedulina y la lipocalina-2 podrían representar alternativas a la puntuación SOFA para detectar sepsis y shock séptico en pacientes quirúrgicos con infección.

Clinical factors influencing mortality risk in hospital-acquired sepsis.

BACKGROUND: Identification of factors that confer an increased risk of mortality in hospital-acquired sepsis (HAS) is necessary to help prevent, and improve the outcome of, this condition. AIM: To evaluate the clinical characteristics and factors associated with mortality in patients with HAS. METHODS: Retrospective study of patients with HAS in a major Spanish Hospital from 2011 to 2015. Data from adults receiving any of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes associated with sepsis were collected. Those fulfilling the SEPSIS-2 definition with no evidence of infection during the first 48 h following hospitalization were included (N = 196). Multivariate analysis was employed to identify the risk factors of mortality. FINDINGS: HAS patients were found to have many of the risk factors associated with cardiovascular disease (male sex, ageing, antecedent of cardiac disease, arterial hypertension, dyslipidaemia, smoking habit) and cancer. Vascular disease or chronic kidney disease were associated with 28-day mortality. Time from hospital admission to sepsis diagnosis, and the presence of organ failure were risk factors for 28-day and hospital mortality. Experiencing more than one episode of sepsis increased the risk of hospital mortality. 'Sepsis code' for the early identification of sepsis was protective against hospital mortality. CONCLUSION: This study identifies several major factors associated with mortality in patients suffering from HAS. Implementation of surveillance programmes for the early identification and treatment of sepsis translate into a clear benefit.